DESCRIPTION: These proposed experiments will combine genetic, cell biological and physiological approaches to study the development and plasticity of neuronal connections. Cultured neurons from Drosophila mutants that express defects in axonal navigation, nerve terminal arborization and synaptic plasticity will be used to focus on studies of the dynamic regulation of the growth cone cytoskeleton, membrane vesicle cycling, and cell adhesion by second messengers and protein kinases. The DIAS analysis system will be used to detect abnormal motility and related behaviors of growth cones from mutant neurons, and a fourth aim will also use DIAS to identify abnormal locomotory behaviors of mutant fly larvae.